ac9b00027_si_003.xlsx (841.74 kB)
Reliable LC-MS Multiattribute Method for Biotherapeutics by Run-Time Response Calibration
dataset
posted on 2019-03-27, 00:00 authored by Zhongqi Zhang, Bhavana Shah, Xiaoyan GuanA major
challenge of a mass-spectrometry-based quantitative multiattribute
method (MAM) for biotherapeutics is its high variability between instruments.
For reproducible attribute measurements, not only is a similar instrument
model required, but the instruments must also be tuned to the same
condition. This poses great long-term challenges, considering the
rapid development of new instrumentations. In addition, differences
in digestion efficiency, peptide recovery, and artificial modifications
during sample preparation also contribute to variability between laboratories.
To overcome these challenges, new mathematical methods are developed
to calculate the attribute abundance in the sample, using the reference
standard (RS) material as calibrant. Most quality attributes in the
RS remain constant throughout the life of the standard, and therefore,
the RS can serve as a calibrant to correct for the difference between
instruments or sample preparation procedures. Because RS data are
usually collected in a MAM assay, no additional work is required from
the analyst. Data from a large number of attributes demonstrated that
these methodologies greatly reduced instrument-to-instrument and sample
preparation variabilities. With these methodologies, a consistent
instrument model and sample preparation procedure is no longer a requirement.
As a result, changes in digestion procedure and advances in instrumentations
will not significantly affect the assay result.